Ultrasound assisted one-pot synthesis and preliminary in vitro studies of salicylamide arylpiperazines as dual 5-HT1A/5-HT7 ligands

In our research to find new dual 5-HT1A/5-HT7 ligands from the long-chain arylpiperazine (LCAP) family, we applied a new synthesis method with the support of ultrasound. The first tests related to the synthesis were carried out on the preparation of approved drugs with arylpiperazine structures such as aripiprazole, trazodone and flibanserin . The results were very satisfactory. In the next stage of the research, we obtained the compounds from the LCAPs group using the sonochemical method, with sali-cylamide in the structure, a flexible / stiffened linker and a fragment of o-methoxyarylpiperazine / m-chloroarylpiperazine. Among the compounds obtained, two selective 5-HT1A / 5-HT7 lig -ands were selected, i.e. 2-((4-((4-(2-methoxyphenyl)piperazin-1-yl)methyl)benzyl)oxy)benzamide ( 18 ) (5-HT1A Ki = 12.6 nM, 5-HT7 Ki = 6.8 nM) and 2-((4-((4-(3-chlorophenyl)piperazin-1-yl)methyl)benzyl)oxy)benzamide ( 23 ) (5-HT1A Ki = 11.6 nM, 5-HT7 Ki = 5.5 nM).(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In our research, we used ultrasound to support a new synthesis method to find dual 5-HT1A/5-HT7 ligands from the long-chain arylpiperazine (LCAP) family. We tested the synthesis method on approved drugs with arylpiperazine structures and achieved satisfactory results. We then obtained compounds from the LCAPs group using the sonochemical method and selected two selective 5-HT1A/5-HT7 ligands.